TBC1D4 is necessary for enhancing muscle insulin sensitivity in response to AICAR and contraction

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Standard

TBC1D4 is necessary for enhancing muscle insulin sensitivity in response to AICAR and contraction. / Kjøbsted, Rasmus; Chadt, Alexandra; Jørgensen, Nicolas Oldenburg; Kido, Kohei; Larsen, Jeppe K; de Wendt, Christian; Al-Hasani, Hadi; Wojtaszewski, Jørgen.

I: Diabetes, Bind 68, Nr. 9, 2019, s. 1756-1766.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Harvard

Kjøbsted, R, Chadt, A, Jørgensen, NO, Kido, K, Larsen, JK, de Wendt, C, Al-Hasani, H & Wojtaszewski, J 2019, 'TBC1D4 is necessary for enhancing muscle insulin sensitivity in response to AICAR and contraction', Diabetes, bind 68, nr. 9, s. 1756-1766. https://doi.org/10.2337/db18-0769

APA

Kjøbsted, R., Chadt, A., Jørgensen, N. O., Kido, K., Larsen, J. K., de Wendt, C., ... Wojtaszewski, J. (2019). TBC1D4 is necessary for enhancing muscle insulin sensitivity in response to AICAR and contraction. Diabetes, 68(9), 1756-1766. https://doi.org/10.2337/db18-0769

Vancouver

Kjøbsted R, Chadt A, Jørgensen NO, Kido K, Larsen JK, de Wendt C o.a. TBC1D4 is necessary for enhancing muscle insulin sensitivity in response to AICAR and contraction. Diabetes. 2019;68(9):1756-1766. https://doi.org/10.2337/db18-0769

Author

Kjøbsted, Rasmus ; Chadt, Alexandra ; Jørgensen, Nicolas Oldenburg ; Kido, Kohei ; Larsen, Jeppe K ; de Wendt, Christian ; Al-Hasani, Hadi ; Wojtaszewski, Jørgen. / TBC1D4 is necessary for enhancing muscle insulin sensitivity in response to AICAR and contraction. I: Diabetes. 2019 ; Bind 68, Nr. 9. s. 1756-1766.

Bibtex

@article{959b6f4dcf2040d888c5052b9ec6f9ac,
title = "TBC1D4 is necessary for enhancing muscle insulin sensitivity in response to AICAR and contraction",
abstract = "Muscle insulin sensitivity for stimulating glucose uptake is enhanced in the period after a single bout of exercise. Recently, we demonstrated that AMPK is necessary for AICAR, contraction and exercise to enhance muscle and whole-body insulin sensitivity in mice. Correlative observations from both human and rodent skeletal muscle suggest that regulation of the phosphorylation status of TBC1D4 may relay this insulin sensitization. However, the necessity of TBC1D4 for this phenomenon has not been proven. Thus, the purpose of this study was to determine if TBC1D4 is necessary for enhancing muscle insulin sensitivity in response to AICAR and contraction. We found that immediately following contraction and AICAR stimulation, phosphorylation of AMPKα-Thr172 and downstream targets were increased similarly in glycolytic skeletal muscle from wild-type and TBC1D4-deficient mice. In contrast, 3 h after contraction or 6 h after AICAR stimulation, enhanced insulin-stimulated glucose uptake was evident in muscle from wild-type mice only. The enhanced insulin sensitivity in muscle from wild-type mice was associated with improved insulin-stimulated phosphorylation of TBC1D4 (Thr649 and Ser711) but not of TBC1D1. These results provide genetic evidence linking signaling through TBC1D4 to enhanced muscle insulin sensitivity following activation of the cellular energy sensor AMPK.",
keywords = "The Faculty of Science, AMPK, Exercise, Glucose uptake, AS160",
author = "Rasmus Kj{\o}bsted and Alexandra Chadt and J{\o}rgensen, {Nicolas Oldenburg} and Kohei Kido and Larsen, {Jeppe K} and {de Wendt}, Christian and Hadi Al-Hasani and J{\o}rgen Wojtaszewski",
note = "CURIS 2019 NEXS 278 {\circledC} 2019 by the American Diabetes Association.",
year = "2019",
doi = "10.2337/db18-0769",
language = "English",
volume = "68",
pages = "1756--1766",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association",
number = "9",

}

RIS

TY - JOUR

T1 - TBC1D4 is necessary for enhancing muscle insulin sensitivity in response to AICAR and contraction

AU - Kjøbsted, Rasmus

AU - Chadt, Alexandra

AU - Jørgensen, Nicolas Oldenburg

AU - Kido, Kohei

AU - Larsen, Jeppe K

AU - de Wendt, Christian

AU - Al-Hasani, Hadi

AU - Wojtaszewski, Jørgen

N1 - CURIS 2019 NEXS 278 © 2019 by the American Diabetes Association.

PY - 2019

Y1 - 2019

N2 - Muscle insulin sensitivity for stimulating glucose uptake is enhanced in the period after a single bout of exercise. Recently, we demonstrated that AMPK is necessary for AICAR, contraction and exercise to enhance muscle and whole-body insulin sensitivity in mice. Correlative observations from both human and rodent skeletal muscle suggest that regulation of the phosphorylation status of TBC1D4 may relay this insulin sensitization. However, the necessity of TBC1D4 for this phenomenon has not been proven. Thus, the purpose of this study was to determine if TBC1D4 is necessary for enhancing muscle insulin sensitivity in response to AICAR and contraction. We found that immediately following contraction and AICAR stimulation, phosphorylation of AMPKα-Thr172 and downstream targets were increased similarly in glycolytic skeletal muscle from wild-type and TBC1D4-deficient mice. In contrast, 3 h after contraction or 6 h after AICAR stimulation, enhanced insulin-stimulated glucose uptake was evident in muscle from wild-type mice only. The enhanced insulin sensitivity in muscle from wild-type mice was associated with improved insulin-stimulated phosphorylation of TBC1D4 (Thr649 and Ser711) but not of TBC1D1. These results provide genetic evidence linking signaling through TBC1D4 to enhanced muscle insulin sensitivity following activation of the cellular energy sensor AMPK.

AB - Muscle insulin sensitivity for stimulating glucose uptake is enhanced in the period after a single bout of exercise. Recently, we demonstrated that AMPK is necessary for AICAR, contraction and exercise to enhance muscle and whole-body insulin sensitivity in mice. Correlative observations from both human and rodent skeletal muscle suggest that regulation of the phosphorylation status of TBC1D4 may relay this insulin sensitization. However, the necessity of TBC1D4 for this phenomenon has not been proven. Thus, the purpose of this study was to determine if TBC1D4 is necessary for enhancing muscle insulin sensitivity in response to AICAR and contraction. We found that immediately following contraction and AICAR stimulation, phosphorylation of AMPKα-Thr172 and downstream targets were increased similarly in glycolytic skeletal muscle from wild-type and TBC1D4-deficient mice. In contrast, 3 h after contraction or 6 h after AICAR stimulation, enhanced insulin-stimulated glucose uptake was evident in muscle from wild-type mice only. The enhanced insulin sensitivity in muscle from wild-type mice was associated with improved insulin-stimulated phosphorylation of TBC1D4 (Thr649 and Ser711) but not of TBC1D1. These results provide genetic evidence linking signaling through TBC1D4 to enhanced muscle insulin sensitivity following activation of the cellular energy sensor AMPK.

KW - The Faculty of Science

KW - AMPK

KW - Exercise

KW - Glucose uptake

KW - AS160

U2 - 10.2337/db18-0769

DO - 10.2337/db18-0769

M3 - Journal article

VL - 68

SP - 1756

EP - 1766

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 9

ER -

ID: 222095228